Collagen is the principal structural protein in the body and constitutes approximately one-third of the total body protein. It comprises most of the organic matter of the skin, tendons, bones and teeth and occurs as fibrous inclusions in most other body structures. Some of the properties of collagen are its high tensile strength; its ion exchanging ability, due in part to the binding of electrolytes, metabolites and drugs; its low antigenicity, due to masking of potential antigenic determinants by the helical structure, and its low extensibility, semipermeability, and solubility. Furthermore collagen is a natural substance for cell adhesion. These properties make this protein suitable for fabrication of bioremodelable research products and medical devices such as implantable prostheses, cell growth substrates, and cellular and acellular tissue constructs.
Collagen compositions are typically prepared from skin or tendons by dispersion, digestion or dissolution, or a combination thereof, of the native tissue collagen. Dispersion involves mechanically shearing the tissue to produce a suspension of collagen fibers. Digestion involves enzyme degradation of the non-helical telopeptide portions of the collagen molecule, resulting in a solution of atelopeptide collagen. Dissolution involves cleavage of acid labile crosslinks in newly formed collagen fibers resulting in a solution of collagen monomers and polymers using procedures involving acid or enzyme extraction. Enzyme extraction is preferable in many instances because its methodology produces increased yield and higher purity collagen. However enzyme extraction suffers the disadvantage of producing partially degraded collagen, i.e., the extraction enzymes cleave the collagen molecule at the terminal non-helical regions which contain the inter-molecular cross-linkages.
Injectable formulations have been used in the art as tissue bulking compositions, particularly in urology and plastic surgery. Upon implantation to a patient, however, the volume persistence of previous implants decreases partly due to the absorption of the aqueous carrier by the body and partly due to the low concentration of the collagen. Follow up or “top-off” injections at the site are usually necessary with previously developed collagen compositions because the volume decreases due to the absorption of liquid component of the composition by the body. Therefor, volume persistence and shape persistence are desired of an injectable collagen implant. Higher concentrations of collagen helps to maintain volume persistence, but at the same time decreases extrudability and intrudability of the composition through a needle and into the patient's tissue.
Besides volume persistence, shape persistence is desired of the injectable collagen compositions known in the art. When injected, the collagen tends to migrate through the tissue; therefore, if specific and local tissue augmentation or bulking is required, such migration would necessitate subsequent injections.
The present invention describes a collagen composition in the form of bioengineered collagen fibers, apparatus methods for making bioengineered collagen fibers and their use as an injectable collagen composition that overcomes the drawbacks of injectable collagen compositions known in the art. Other preferred embodiments directed to bioengineered collagen fibers formed into a matrix substrate for cell culture and a composition comprising compacted fibers for surgical implantation are also disclosed.